PXD043846-1

PXD043846 is an original dataset announced via ProteomeXchange.

Title	ProNGF elicits retrograde axonal degeneration of basal forebrain neurons via p75NTR and induction of APP
Description	Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple targets in the brain to regulate cognitive functions, and are compromised in numerous neurodegenerative disorders. Our previous study showed that injury to the target region of these neurons affects their viability in vivo. Moderate cortical injury in mice promoted a significant increase in proneurotrophins in the injured cortex, leading to the retrograde loss of BFCNs ipsilateral to the injury via the p75 neurotrophin receptor (p75NTR). We determined that stimulation of BFCN axon terminals with proNGF elicited retrograde degeneration of the axons leading to cell death of these neurons in vitro. Our current study investigates mechanisms of axonal p75NTR signaling, and shows that retrograde transport and local axonal protein synthesis are necessary for proNGF induced retrograde degeneration initiated at the axon terminal. Analysis of the nascent axonal proteome revealed numerous newly synthesized proteins after stimulation of axon terminals with proNGF. Pathway analysis showed that amyloid precursor protein (APP) was a key upstream regulator. Our results show a functional role for APP in promoting proNGF induced BFCN axonal degeneration and cell death.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_10:51:40.371.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043846
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Tong Liu
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-17 09:00:36	ID requested
⏵ 1	2025-05-06 10:51:41	announced

10.6019/PXD043846;

Dasgupta S, Pandya MA, Zanin JP, Liu T, Sun Q, Li H, Friedman WJ, and induction of amyloid precursor protein. Sci Signal, 17(855):eadn2616(2024) [pubmed]

10.1126/scisignal.adn2616;

submitter keyword: Key words: proneurotrophin, axon degeneration, p75NTR, axonal protein synthesis

Wilma Friedman
contact affiliation	Department of Biological Sciences Rutgers University Newark
contact email	wilmaf@newark.rutgers.edu
lab head
Tong Liu
contact affiliation	Rutgers University
contact email	linto@njms.rutgers.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD043846

PRIDE project URI

• PRIDE
  1. PXD043846
     1. Label: PRIDE project
     2. Name: ProNGF elicits retrograde axonal degeneration of basal forebrain neurons via p75NTR and induction of APP